Hypoadrenal Disorders

Question 1

Number of carbons in cholesterol?

Answer 1

27

Question 2

Pathway for aldosterone production from cholesterol?

Answer 2

Cholesterol -> 11deoxycorticosteron -> corticosterone -> aldosterone

Question 3

Pathway for sex steroids production from cholesterol?

Answer 3

Progesterone -> 17hydroxyprogesterone -> sex steroids

Question 4

Pathway for cortisol production from cholesterol?

Answer 4

Progesterone -> 17hydroxyprogesterone -> 11deoxycortisol -> cortisol

Question 5

What molecule is produced from adding OH to C21, 11 and 18

Answer 5

aldosterone

Question 6

What molecule is produced from adding OH to C17, 21 and 11

Answer 6

cortisol

Question 7

which carbons are hydroxylated to produce aldosterone

Answer 7

C21, 11 and 18

Question 8

which carbons are hydroxylated to produce cortisol

Answer 8

C17, 21 and 11

Question 9

Non specific causes of ADRENOCORTICAL FAILURE? (2)

Answer 9

1. Adrenal glands destroyed

2. Enzymes in the steroid synthetic pathway not working

Question 10

CAUSES OF ADRENOCORTICAL FAILURE (SPECIFIC): (3)

Answer 10

• Tuberculosis Addison’s disease (COMMONEST WORLDWIDE)
• Autoimmune Addison’s disease (COMMONEST IN UK)
• Congenital adrenal hyperplasia

Question 11

CONSEQUENCES OF ADRENOCORTICAL FAILURE:? (6)

Answer 11

• Fall in BP Loss of sodium (+water)
• Loss of salt in the urine
• Increased plasma potassium Loss of Na+/K+ exchanger
• Fall in glucose due to glucocorticoid deficiency
• High ACTH resulting in increased pigmentation ACTH co-secreted with MSH
• Eventual death due to hypotension

Question 12

What is POMC

Answer 12

Synthesised in the pituitary and broken down into ACTH and MSH (and endorphins and enkephalins and other peptides)

Question 13

Test for Addison? (3)

Answer 13

• 9am cortisol Low
• ACTH High Attempting to make adrenal glands release more cortisol
• Short synacthen test (synACTHen= synthetic ACTH) Give 250ug synacthen intramuscularly Measure cortisol response A normal person will release more cortisol, but someone with Addison’s won’t

Question 14

What enzyme does the side chain cleavages in cholesterol product synthesis

Answer 14

P450 scc

Question 15

CONGENITAL ADRENAL HYPERPLASIA:

 Most commonly caused by ….

Answer 15

21-hydroxylase deficiency

Question 16

COMPLETE 21-HYDROXYLASE DEFICIENCY results in …

Answer 16

No aldosterone or cortisol Can’t survive without these for more than 24hrs

Question 17

Foetal survival with COMPLETE 21-HYDROXYLASE DEFICIENCY?

Answer 17

• Foetuses can survive in the placenta with maternal aldosterone and cortisol, but not after birth -> BP drops rapidly

Question 18

Symptoms of COMPLETE 21-HYDROXYLASE DEFICIENCY in foetus? how to spot a foetus with it?

Answer 18

• Get excessive sex steroid synthesis Girls hard to identify sexuality- labial fusion and cliteromegaly (virilised) Sexual ambiguity is a key sign

Question 19

Treatment for COMPLETE 21-HYDROXYLASE DEFICIENCY

Answer 19

Suppress ACTH, minimise excessive hormones, (surgically correct anatomical features Girls only), saline

Question 20

How do neonates present with COMPLETE 21-HYDROXYLASE DEFICIENCY

Answer 20

As a neonate with a salt losing Addisonian crisis

Question 21

What is Addisons disease

Answer 21

Adrenocortical failure to produce aldosterone and cortisol

Question 22

Why does 11-HYDROXYLASE DEFICIENCY not result in hypotension?

Answer 22

No salt losing crisis (hypotension) because 11 deoxy corticosterone can act similarly to aldosterone

Question 23

Symptoms of 11-HYDROXYLASE DEFICIENCY (5)

Answer 23

• High BP due to sodium retention
• Virilisation due to excess sex steroids
• Low potassium
• Excess sex steroids and testosterone and 11-deoxycorticosterone
• Deficient cortisol and aldosterone

Question 24

17-HYDROXYLASE DEFICIENCY: results in (levels of XYZ hormones)?

Answer 24

• Cortisol and sex steroid deficiency

- Excess mineralocorticoids (11-deoxycorticosterone and aldosterone)

Question 25

Problems with 17-hydroxylase deficiency?

Answer 25

hypertension, low K, sex steroid deficiency, glucocorticoid deficiency (low glucose)